7. Project Summary/Abstract This proposal seeks to understand the interaction between air pollution and psychosocial stress on markers of inflammation and subclinical cardiovascular disease (CVD). Under the mentorship of Dr. Joel Kaufman, this training and research plan will build upon Dr. Hajat's expertise in social epidemiology and prepare her for a career studying the nexus of social and environmental factors and their impact on CVD. During the K99 phase, Dr. Hajat will use didactic instruction and independent study to gain additional training in 1) the biology of stress and CVD 2) spatial statistical methods and 3) exposure generation and assessment. This training will provide Dr. Hajat with interdisciplinary skills and knowledge as she moves towards an independent research career. During the K99 phase Dr. Hajat will characterize the extent to which biomarkers of stress, neighborhood-level psychosocial stressors and individual level psychosocial stressors are spatially correlated with ambient air pollutants, specifically particulate matter <2.5 m in aerodynamic diameter, nitrogen dioxide, oxides of nitrogen and black carbon. This work will build upon Dr. Hajat's previous work using the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study of subclinical CVD in a cohort of older adults recruited from six metropolitan areas across the US. Upon completion of the training phase of this award, Dr. Hajat will undertake research during the R00 phase of the project that will transition her to an independent investigator. The aims of this research are (1) to assess the synergistic effects of air pollution and psychosocial stress (measured objectively and subjectively) on markers of inflammation (C-reactive protein, interleukin-6 (IL-6) and fibrinogen) as well as on the progression of atherosclerosis in different vascular beds, measured by intima media thickness, coronary calcification and ankle brachial index and (2) to conduct a crossover study which exposes participants to both diesel exhaust (DE) from an inhalation facility and a laboratory-based mental stress test to assess the synergistic effect of both exposures on physiological outcomes such as blood pressure, heart rate variability, catecholamine levels and IL-6. The research in the R00 phase proposes epidemiologic studies of two complementary extant data sources, MESA and the National Health and Nutrition Examination Survey, a cross-sectional nationally representative sample of the US population. Both studies have data on air pollution, psychosocial stressors, inflammation and subclinical CVD and together capture a larger geographic area and populations across the life course. The R00 phase also proposes conducting an experimental study. The study will be conducted in one of the nation's few controlled inhalation facilities where subjects will be exposed to both DE and a laboratory generated acute mental stressor. The acute mental stress exposure, which is often used in psychology, will consist of administering a speech task and an arithmetic task. Understanding the synergistic effects of air pollution and psychosocial stress will help advance our understanding of the biological mechanisms behind environmental health disparities.